Systems and methods for selective coating removal for resorbable metal medical devices

ABSTRACT

The invention relates to self-assembled organosilane coatings for resorbable medical implant devices. The coatings can be prepared from coating compositions containing organosilane and can be applied to metal or metal alloy substrates. Prior to applying the coatings, the surfaces of the substrates can be pretreated. The coatings can be functionalized with a binding compound that is coupled with an active component. The coatings can be selectively removed, e.g., patterned, to expose portions of the uncoated substrate. Selecting different patterns can provide the ability to regulate or control various properties, such as, corrosion and hydrogen generation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. Non-Provisional patentapplication Ser. No. 16/073,017, entitled “SYSTEMS AND METHODS FORSELECTIVE COATING REMOVAL FOR RESORBABLE METAL MEDICAL DEVICES”, filedon Jul. 26, 2018, which is a U.S. National Stage Application under 35U.S.C. § 371 of International Application No. PCT/2017/016347, filed onFeb. 3, 2017, which claims priority under 35 U.S.C. § 119(e) from U.S.provisional patent application No. 62/290,555, filed on Feb. 3, 2016,both of which are entitled “SYSTEMS AND METHODS FOR SELECTIVE COATINGREMOVAL FOR RESORBABLE METAL MEDICAL DEVICES,” the contents of which areincorporated herein by reference.

GOVERNMENT SUPPORT

This invention was made with government support under Grant No.EEC0812348 awarded by the National Science Foundation (NSF). Thegovernment has certain rights in the invention.

FIELD OF THE INVENTION

The present invention relates to self-assembled organosilane-containingcompositions, methods of preparing the compositions, systems and methodsof depositing/applying the compositions on substrates to form coatingsand selectively removing a portion of the coatings, e.g., patterning, tocontrol or tune properties, including but not limited to, corrosion. Theinvention also relates to uses for the partially coated substrates asmedical implant devices.

BACKGROUND OF THE INVENTION

Every year millions of orthopedic and craniofacial surgical proceduresare performed in the United States, which require placement of metal,e.g., stainless steel or titanium, hardware in a patient body. Afterbone healing is complete, these metal implant devices are no longerneeded. The devices can be left in situ or, alternatively, they can beremoved. Each of these alternatives has disadvantages or problemsassociated therewith. For example, leaving the hardware in situincreases the chances of infection and rejection, and removal of thehardware requires a second surgery and causes a risk of infection, painand discomfort to the patient, as well as it being an additionalexpense. To overcome these disadvantages or problems, there has beendeveloped a number of resorbable polymeric devices that are effective todegrade over a period of time. Thus, the device does not remain in-situand there is no need to surgically remove the device because when thedevice is no longer needed, the polymeric material degrades or dissolveswithin the patient body. However, there are also disadvantagesassociated with the resorbable polymer devices. For instance, it hasbeen found that the resorbable polymeric materials, which are used forthe construction of biodegradable medical implant devices, can lackmechanical strength as compared to that exhibited by metal implants andhave a limited set of applications. As a result, there is an interest inthe art to identify materials that degrade over time while demonstratingsufficient mechanical strength prior to degradation.

It has been found that the development of new technologies forimplantable devices based on resorbable magnesium and magnesium alloyshas the potential to make a significant clinical impact. Magnesium andmagnesium alloys are suitable materials for the construction ofresorbable devices because they have mechanical properties compatible tobone and can be resorbed over a period of time. However, there are otherproperties of magnesium and magnesium alloys that are problematic fortheir use as medical implant devices. For example, magnesium is nottypically used in the fabrication of medical implant devices primarilybecause the corrosion of magnesium results in the production ofhydrogen. Medical implant devices constructed of magnesium can cause theaccumulation of hydrogen in areas surrounding the device and thus,result in the formation of gas cavities in the patient body. In orderfor magnesium and magnesium alloys to be considered as suitablematerials for use in constructing medical implant devices, the rate ofcorrosion of these materials needs to be closely monitored andcontrolled to prevent formation of gas cavities. Thus, there are anumber of important characteristics that have to be controlled in orderto achieve the best clinical outcomes including, for example, rate ofresorption, control of corrosion products, tissue integration andosteoconduction properties of the device.

It is known to deposit a coating composition on the surface of metalimplant devices to modify the properties, e.g., corrosion, of thedevices. Coatings for metal-based implants have been classified asconversion or deposition coatings. Conversion coatings are generallyformed in situ through a reaction between the substrate and itsenvironment, and are typically inorganic. For application to magnesiumor magnesium alloys, these coatings are often composed of oxides,phosphates or fluorides. Conversion coatings typically advantageouslyexhibit good adhesion to the substrate, however, there are disadvantagesassociated with mechanical durability and biocompatibility of thesecoatings. Deposition coatings are typically organic or ceramic and areapplied through physical interactions with the surface of a metalsubstrate. For application to magnesium or magnesium alloy substrates,deposition coatings often require a conversion coating pre-treatment toimprove adhesion to the alloy substrates. In the absence of a conversioncoating pre-treatment, e.g., one-step coatings, it is likely that thecoated substrate will demonstrate poor adhesion and corrosionprotection.

There is a desire in the art to develop a mechanism for controlling therates of corrosion of magnesium and magnesium alloy in order to reduceor minimize the production and accumulation of hydrogen resultingtherefrom, and to construct medical implant devices from materials thatdemonstrate sufficient mechanical strength when needed and degradationover time when no longer needed. Further, there is a desire to develop acoating that is effective to control rates of corrosion of magnesium andmagnesium alloy and to reduce or minimize the production andaccumulation of hydrogen resulting therefrom, and demonstrates goodadherence or adhesion to the magnesium and magnesium alloy. Moreover, itwould be advantageous for the coatings to be capable of being customizedor modified to allow properties, such as, corrosion and hydrogengeneration, to be tuned or regulated.

SUMMARY OF THE INVENTION

An object of the present invention is to develop novel coatingcompositions for application to magnesium and magnesium alloy substratesfor use as medical implant devices. In particular, an object of thepresent invention is to develop hybrid bio-inspired anticorrosivecoatings based on self-assembled multilayer organosilane. The surface ofthese coatings can be modified via covalent bonding with an activecomponent, including bioactive molecules, such as proteins and peptides.These surface chemistry modifications can provide the ability to controldifferent physical chemical properties of the coatings, including butnot limited to, hydrophobicity and charge, as well as bioactivity. Thesecoatings can effectively control the degradation rate of magnesium andmagnesium alloy resorbable devices to insure safety and efficiency, andto induce desirable tissue responses. Further, these coatings can befunctionalized to regulate the rate of corrosion and insure the deviceintegration into target tissues. Furthermore, these coatings can beselectively removed, e.g., patterned, to expose portions of uncoatedsubstrate, which can be effective to regulate pre-selected properties,such as, but not limited to corrosion rate.

In one aspect, the invention provides a medical implant device includinga magnesium or magnesium alloy substrate, having a first surface and anopposing second surface; a self-assembled organosilane-containingcoating applied to at least one of the first and second surface; and apattern applied to the coating on at least one of the first and secondsurfaces. The pattern includes one or more areas of selective removal ofthe coating from the substrate. Further, a binding compound can becombined with the coating and furthermore, an active component can becoupled to the binding compound.

In certain embodiments, a binding compound is combined with the coating.Furthermore, an active component can be coupled to the binding compound.

The device can also include a pretreatment applied to the at least oneof the first and second surfaces, and the coating applied to thepretreatment.

In certain embodiments, a first portion of the pattern has a firstconfiguration and a second portion of the pattern has a different,second configuration.

The one or more areas of selective removal of the coating is effectiveto increase the corrosion rate of the substrate.

In another aspect, the invention provides a method of forming apatterned coating on a medical implant device. The method includesobtaining a uncoated substrate having a top surface and an opposingbottom surface; preparing a coating composition including organosilane;applying the coating composition to at least one of the top and bottomsurfaces of the uncoated substrate to form a coating thereon; andselectively removing a portion of the coating to expose the uncoatedsubstrate.

The method can further include functionalizing the coating with abinding compound, and coupling an active component to the bindingcompound.

The step of selectively removing can include a process selected from thegroup consisting of laser ablation, ion etching, electron beam etchingand combinations thereof. The selective removal of a portion of thecoating forms a pattern exposing one or more areas of the uncoatedsubstrate. Furthermore, one or more of the size, density and spatialdistribution of the one or more areas of the uncoated substrate iscontrolled to regulate a pre-selected property, such as, corrosion rate.

In certain embodiments, a portion of the coating is selectively removedto expose the uncoated substrate on both of the top and bottom surfaces.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic that shows various patterns formed by selectivelyremoving a coating deposited on a magnesium or magnesium alloy substrateto expose portions of uncoated substrate for use in regulating corrosionrate, in accordance with certain embodiments of the invention;

FIG. 2 shows SEM micrographs A, B and C of laser ablated substratesamples at various magnifications, i.e., A is low magnification, B isintermediate magnification and C is high magnification, wherein thecoating is completely removed in the ablated areas and the underlyingmetal remains intact, in accordance with certain embodiments of theinvention;

FIG. 3 is a plot of hydrogen evolution verses time (i.e., days) forpatterned Mg—OH-AS coated substrate samples, in accordance with certainembodiments of the invention; and

FIG. 4 is a SEM micrograph that shows a patterned magnesium disk exposedto simulated body fluid (SBF) for a period of seven days with a bare Mgside on the left and AS coated on the right, and wherein insets show anEDS spectra from the respective areas, in accordance with certainembodiments of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention generally relates to self-assembledorganosilane-containing coating compositions applied to, or depositedon, substrates to form patterned coatings; and methods ofapplying/depositing the coating compositions onto the substrates, andsubsequently selectively removing a portion or part of the coatings toexpose the uncoated substrates (e.g., underneath the coatings). Theinvention also relates to the use of the patterned coated substrates inconstructing and fabricating medical implant devices for use in varioussurgical applications, such as, but not limited to, dental, orthopedic,craniofacial, and cardiovascular.

The substrates, e.g., medical implant devices, can be composed of a widevariety of materials that are known in the art for such purposes. Inaccordance with the objectives of controlling the rates of corrosion ofthe substrates in order to reduce or minimize the production andaccumulation of hydrogen resulting therefrom, and to construct medicalimplant devices from materials that demonstrate sufficient mechanicalstrength when needed and degradation over time when no longer needed, itis preferred that the substrates, e.g., medical implant devices, becomposed of magnesium or magnesium alloy.

In certain embodiments, the coating composition is directly applied to,or deposited on, the surface of the substrate, e.g., medical implantdevice, in the absence of any pretreatment or pre-coating of thesurface, to form a coating thereon. However, in other embodiments, forthe purpose of improving the adherence and/or adhesion of the coating tothe surface of the substrate, a pretreatment or pre-coating is appliedto the surface of the substrate prior to applying the coatingcomposition. Suitable pretreatments or pre-coatings include those knownin the art for use with magnesium or magnesium alloy substrates toimprove adherence and/or adhesion of a coating to the surface of thesubstrates.

Following the application of the coating composition and formation ofthe resultant coating on the surface of the substrate, the coating ispartially removed. The partial removal of the coating from the surfaceof the substrates can be selectively conducted by forming variouspatterns of coated and uncoated substrate. In certain areas of thepattern, the uncoated surface of the substrate is exposed and in otherareas, the surface has the coating applied thereto. The selectiveremoval, e.g., pattern, can be effective to regulate or control certainproperties of the substrate, such as, corrosion rate and hydrogengeneration.

Without intending to be bound by any particular theory, it is believedthat the patterned coatings are effective to modify various propertiesand characteristics of the underlying magnesium/magnesium-containingsubstrate of the a medical implant device. For example, a patternedcoating can be effective to control one or more of the followingproperties of the magnesium/magnesium-containing substrate: corrosionrate, production/accumulation of hydrogen, rate of resorption, tissueintegration and osteoconduction. In certain embodiments, the patternedcoating can be effective to reduce or preclude the corrosion rate and,in turn, the production/accumulation of hydrogen. Further, the surfaceof the coated portions of the substrate can include covalent bondingwith different molecules, including bioactive molecules, such asproteins and peptides.

Surface chemistry modifications can provide the ability to controldifferent physical chemical properties of the coating, including but notlimited to, hydrophobicity and charge, as well as bioactivity.Furthermore, the patterned, substrate surface including coated anduncoated portions or parts can be used to control or regulatepre-selected or desired properties.

Conventional apparatus and techniques are generally known for preparingand applying/depositing a silane coating composition onto a substrate,modifying or functionalizing the surface of the formed silane coating,and selectively removing a portion of the coating formed. For example,various amphiphilic organosilanes are used to form nanostructured filmsfor glass coating applications, and the application of organosilanes forcorrosion control are known. However, there is a need in the art todevelop organosilane-containing compositions for use in coatingresorbable metallic, e.g., magnesium and magnesium alloy, substrates,such as medical implant devices. In particular, the coatings for medicalimplant devices require special properties, including the ability toadapt to the intrinsically unstable physical and chemical environment ofa corroding metal substrate, as well as the ability to be functionalizedwith bioactive molecules.

In general, self-assembled coatings, e.g., monolayers, are thin filmsproduced by deposition of materials, such as, organosilanes. Thecoatings are formed, e.g., spontaneously, on a surface of a substrate byadsorption and include a head group, tail and functional end groups. Thehead group can be in a vapor phase or a liquid phase. The head groupassembles onto the substrate surface, while the tail group organizes andassembles farther from the surface of the substrate. The substrate andhead group are selected to react with each other. In certainembodiments, a hydrophilic end (e.g., head group) may bond with thesubstrate surface while a hydrophobic end may be opposite thehydrophilic end.

In accordance with the invention, the self-assembled coatingcompositions include organosilane, such as, hybrid organosilanes. Incertain embodiments, the coating compositions include amphiphilicorganosilanes having an aliphatic tail containing a backbone of 4 to 20carbon atoms (i.e., C4 to C20) and a silane head. A non-limiting exampleof suitable organosilanes include alkylsilanes, such as,alkyltrialkoxysilanes including, but not limited to,decyltriethoxysilane. In certain embodiments, the alkyltrialkoxysilanes,such as, but not limited to, decyltriethoxysilane, are co-polymerizedwith another polymer component, such as, but not limited to,tetramethoxysilane (TMOS). Further, in certain embodiments, thealkyltrialkoxysilanes are combined with a crosslinking material, suchas, but not limited to, a UV crosslinking agent.

The self-assembled coating compositions are applied or deposited ontothe magnesium or magnesium alloy surface, e.g., of the medical implantdevice. The magnesium alloy may be selected from a wide variety ofmagnesium alloys known in the art for constructing medical implantdevices. Non limiting examples of suitable magnesium alloys includethose magnesium-containing compositions described in PCT Applicationhaving International Application No. PCT/US2012/058939 entitled“Biodegradable Metal Alloys” filed on Oct. 5, 2012, published asUS20140248288 on Sep. 4, 2014, and issued as U.S. Pat. No. 9,510,932 onDec. 6, 2016, and based on U.S. Provisional Patent Application61/544,127 entitled “Biodegradable Metal Alloys” filed on Oct. 6, 2011,which are incorporated in their entirety herein by reference.

In certain embodiments, the magnesium alloys include elemental magnesiumand one or more other elemental components, such as, but not limited to,iron, zirconium, manganese, calcium, yttrium and zinc. The amount ofeach of the components can vary and, in general, the amounts areselected such that the resulting magnesium alloys are within acceptablenon-toxic limits, sufficiently biocompatible and degradable over aperiod of time.

In general, the self-assembled organosilane coatings can be formed usingknown apparatus and conventional coating techniques, including, but notlimited to, physical vapor deposition, electro-deposition orelectro-less deposition. For example, a self-assembled coating can beformed on a magnesium or magnesium alloy substrate at ambient conditionsby spinning, dipping or spraying techniques, which are known in the art.In certain embodiments, a coating is formed by employing a deep-coatingprocess at ambient conditions. This process includes combiningorganosilane and solvent, e.g., water, to form a solution and applyingthe solution to a magnesium or magnesium alloy substrate bydipping/immersing the substrate into a bath of the solution. Theimmersion can be for a time period ranging from minutes to hours and,typically includes sufficient time to allow the organosilane to bond tothe substrate. As previously described, the solution can be applieddirectly to the substrate (in the absence of pretreating or pre-coating)or the solution can be applied to a pretreated or pre-coated substrate.Subsequent evaporation of the solvent, by conventional methods, inducesthe organosilane to self-assemble into micro- or nano-structures andthin film. The resulting coating, e.g., thin film, is rigid, uniform andhas a thickness that can vary from about 100 nanometers to tens ofmicrometers

The coating thickness can depend on various factors including theorganosilane composition components, the process conditions and theintended use of the coated substrate. In one embodiment, the coating hasa thickness of about 1 um. Further, the coating, e.g., laminarstructure, can include multiple layers. In certain embodiments, thecoating may be composed of about 30 nm thick layers. Furthermore, thecoating can be hydrophobic which may be particularly beneficial forcardiovascular applications.

The coating process in accordance with the invention can optionallyinclude pre-treating or pre-coating the surface of the substrate priorto applying/depositing the organosilane coating composition thereto. Thepre-treatment or pre-coating is applied to, or deposited on, the bare,e.g., uncoated, surface of the magnesium or magnesium alloy substrate.The pre-treatment/pre-coating step can vary and may be selected fromknown pretreatment compounds/compositions, techniques and processes thatare employed to improve adherence or adhesion of a coating to thesurface of a substrate. In certain embodiments, the pretreatmentincludes polishing and/or etching the uncoated substrate with nitricacid, and/or passivating with sodium hydroxide. Without intending to bebound by any particular theory, it is believed that pretreating thesubstrate prior to applying the coating composition, e.g., solution,results in a more uniform coating having improved adhesion or adherenceproperties, as compared to coatings that are formed in the absence ofpretreating the substrate.

The coating in accordance with the invention has numerous advantages ascompared to conventional coatings, including, but not limited to, forexample, tunability and controllability. The thickness of the coatingand its mechanical properties can be tuned or controlled. For example,using organosilanes with UV crosslinkable groups provides the ability toincrease stiffness simply by exposure to a UV source. Further,copolymerizing organosilanes with tetramethoxysilane producesliquid-like coatings having increased flexibility, which may beparticularly useful for cardiovascular applications.

Furthermore, the surface of the coatings can be modified orfunctionalized to attach or bind an active component. A bindingcompound, such as, but not limited to amine, carboxyl, thiol, hydroxyland mixtures thereof, is used to bind one or more active components tothe coatings. In certain embodiments, the binding compound is attachedto the surface of the coating. For example, a plurality of moleculescontaining silane groups, e.g., aminosilanes, such as, but not limitedto aminopropyl-trimethoxysilane, can be covalently attached to thesurface of the coating to provide chemistry for attachment of the activecomponent, such as, but not limited to alkaline phosphatase, or formodifying hydrophobicity of the surface. In certain other embodiments,the binding compound can be permeated or encapsulated within thecomposition that is applied to the substrate to form the coating.

As used herein, the term “active component” and related terms refer toat least one molecule, compound, complex, adduct and/or composite thatexhibits one or more beneficial activities, such as, therapeuticactivity, diagnostic activity, biocompatibility, corrosion-resistance,and the like. Active components that exhibit a therapeutic activity caninclude bioactive agents, pharmaceutically active agents, drugs and thelike. Non-limiting examples of bioactive agents include, but are notlimited to, bone growth promoting agents, such as growth factors, drugs,proteins, antibiotics, antibodies, ligands, DNA, RNA, peptides, enzymes,vitamins, cells and the like, and combinations thereof.

With the binding of one or more active components, the coatings andcoated magnesium or magnesium alloy substrates, can be effective tocombine anti-corrosion properties with bioactive surface modifications,which can facilitate improved tissue integration and induce desiredbiological responses in resulting medical implant devices.

Moreover, the coatings, e.g., thin films, formed as a result of theself-assembled coating compositions applied or deposited onto themagnesium or magnesium alloy surface, e.g., of the medical implantdevice, can be partially, e.g., selectively, removed to regulate orcontrol various properties, such as, corrosion. The selective removal ofthe coating to expose portions or parts underneath, e.g., uncoatedsubstrate, can be performed by employing various conventional techniquesand apparatus known in the art. For example, selective removal of acoating can be conducted using one or more of laser ablation, ionetching and electron beam etching. In certain embodiments, the selectiveremoval can include forming various patterns in the coating. Thepatterns can include a plurality of lines or grooves. The number, widthand configuration of the lines or grooves can vary, and may correspondto, or depend on, a pre-determined amount of exposed uncoated surfacenecessary to achieve pre-selected or desired properties. Further, thepattern can be formed on one or more surfaces of the substrate. Forexample, wherein the substrate has upper and lower surfaces, the patterncan be formed on one or both of these surfaces.

Without intending to be bound by any particular theory, it is believedthat selective removal of the coating eliminates inhibition of thecorrosion in the exposed areas of the substrate and increases the rateof corrosion. By changing size, density and spatial distribution ofexposed areas of the substrate, the corrosion rate of the entiresubstrate, e.g., medical implant device, or portions or parts thereofcan be controlled or tuned.

FIG. 1 is a schematic showing a plurality of coated substrates A, B, C,D and E, having a given surface area and various removal patterns formedby lines, e.g., grooves, applied to the surface. As shown in FIG. 1,substrate B has a greater density of grooves, e.g., a higher number ofgrooves or less spacing between the grooves, in the pattern as comparedto substrate A. Substrate C has a greater density of grooves in thepattern as compared to both substrates A and B. In substrate A, thereare four, 1-um wide grooves spaced apart by a distance of 100 um.Substrate B has five grooves and shows a spacing of 50 um, and substrateC has 11 grooves with a spacing of 25 um. An increase in the density,e.g., higher number of grooves or less spacing between the grooves,results in an increase in the exposed area of the uncoated substrate andtherefore, an increase in the rate of corrosion. A similar effect may beachieved by varying the width of the exposed areas, e.g., grooves,without changing their density. In FIG. 1, substrates D and E show thatthe rate of corrosion can be spatially regulated in different portionsor parts, e.g., of a medical implant device, by having the density ofthe grooves be different for certain portions or parts. That is, thepattern for substrate D has a lesser density of grooves on the left-sideportion of the disk and a greater density of grooves toward the rightside portion of the disk. From left to right, the spacing is shown todecrease from 100 um to 25 um. Similarly, the pattern for the screw Ehas a lesser density of grooves at the top portion of the shaft and agreater density of grooves toward the lower portion of the shaft. Fromtop to bottom, the spacing is shown to decrease from 100 um to 25 um.

Patterned, organosilane-coated, magnesium or magnesium-containingsubstrates, in accordance with the invention, are generally effectivefor tissue regeneration and, in particular, bone regeneration, within abody of a patient. These substrates can be employed as materials ofconstruction for various medical implant devices. Non-limiting examplesof suitable medical devices include, but are not limited to, scaffolds,plates, meshes, staples, screws, pins, tacks, rods, suture anchors,tubular mesh, coils, x-ray markers, catheters, endoprostheses, pipes,shields, bolts, clips or plugs, dental implants or devices, such as butnot limited to occlusive barrier membranes, graft devices, bone-fracturehealing devices, bone replacement devices, join replacement devices,tissue regeneration devices, cardiovascular stents, nerve guides,surgical implants and wires.

It will be appreciated by those skilled in the art that changes can bemade to the embodiments described above without departing from the broadinventive concept thereof. It is understood, therefore, that thisinvention is not limited to the particular embodiments disclosed and thefollowing examples conducted, but it is intended to cover modificationsthat are within the spirit and scope of the invention.

EXAMPLES Example 1—Patterning of Coated Mg Samples

A plurality of Mg—OH-AS (wherein AS represents alkylsilane) coatedsubstrate samples were patterned with the use of laser ablation. Several0.2 mm-wide lines were etched on each of the top and bottom surfaces ofAS-coated disks by laser ablation (as shown in views A, B and C of FIG.2). The laser ablation was conducted using a low energy setting suchthat the treatment removed only the AS coating and the underlyingsubstrate remained intact.

Example 2—Hydrogen Evolution

Four experimental groups of three samples each were assembled,including: (a) bare Mg—OH disks (absent of a coating), (b) Mg—OH-AScoated disks with 6-line patterns, (c) Mg—OH-AS coated disks with 4-linepatterns, and (d) fully-coated Mg—OH-AS disks (absent of a pattern).Hydrogen evolution experiments were conducted over a seven-day period.As shown in FIG. 3, the results of these experiments demonstrated thatthe presence of patterning increased the corrosion rate of the Mg—OH-ASsamples (i.e., (b) and (c)) as compared to the Mg—OH-AS sample absent ofpatterning (i.e., (d)). However, the rate of corrosion was significantlylower for the patterned substrates (i.e., (b) and (c)) as compared tothe bare Mg—OH substrate (i.e., (a)). The differences among the fourgroups were highly statistically significant (p<0.0001). Furthermore,the initial corrosion burst was prevented in the patterned Mg—OH-ASsamples (i.e., (b) and (c)). These results demonstrate that thecorrosion rate of the substrate, e.g., medical implant device, can befine-tuned by partial removal of the coating from the substrate.

Example 3—Prevention of Calcium Phosphate Deposition

It was determined that local pH increase in an area around the corrodingMg devices led to spontaneous calcium phosphate precipitation. This is ahighly undesirable outcome, especially in cardiovascular applications(e.g., stents and other devices). The present data indicated that the AScoatings effectively prevented calcium phosphate precipitation andtherefore, may be effective to reduce calcium phosphate formation in thearea of a medical implant device constructed of the substrate inaccordance with the invention.

Example 4—Elemental Analysis

Elemental analysis of the patterned Mg samples containing AS coated andnon-coated areas was conducted and revealed the presence of calcium andphosphate on exposed areas while these elements were not detected on thecoated areas (see FIG. 4). The results of the elemental composition areshown in Table 1 below.

TABLE 1 The elemental composition of the AS coated and uncoated areas ofa Mg sample Element Corroded Area Coated Area K edge Weight % Atomic %Weight % Atomic % O 48.79 62.24 25.81 35.57 Mg 29.69 24.93 50.88 46.14 P8.76 5.77 — — Cl 8.57 4.93 — — Ca 4.19 2.13 — — Si — — 23.31 18.30

We claim:
 1. A method of forming a patterned coating on a medicalimplant device, comprising: obtaining an uncoated substrate having a topsurface and an opposing bottom surface; preparing a coating compositioncomprising organosilane; applying the coating composition to at leastone of the top and bottom surfaces of the uncoated substrate to form acoating thereon; and selectively removing a portion of the coating toexpose the uncoated substrate.
 2. The method of claim 1, furthercomprising functionalizing the coating with a binding compound.
 3. Themethod of claim 2, further comprising coupling an active component tothe binding compound.
 4. The method of claim 1, wherein the selectivelyremoving includes a process selected from the group consisting of laserablation, ion etching, electron beam etching and combinations thereof.5. The method of claim 1, wherein the selectively removing a portion ofthe coating forms a pattern exposing one or more areas of the uncoatedsubstrate.
 6. The method of claim 5, wherein one or more of the size,density and spatial distribution of the one or more areas of theuncoated substrate is controlled to regulate a pre-selected property. 7.The method of claim 6, wherein the property is corrosion rate.
 8. Themethod of claim 1, wherein the selectively removing a portion of thecoating to expose the uncoated substrate is performed on both of the topand bottom surfaces.